Significant challenges are presented by the use of non-autologous tissue in bioprosthetic implants. Chief among the challenges are preventing immunological rejection of the bioprosthetic implant by the host and calcification of the tissue, which results in the undesirable stiffening and degradation of the tissue. Immunological rejection and calcification are particularly problematic for bioprosthetic heart valves, as calcification of valve leaflets after implantation will adversely affect its ability to maintain a one-way flow of blood and prevent undesirable leaking or regurgitation of blood.
Glutaraldehyde has long been the reagent of choice for fixing and sterilizing tissue intended for bioprosthetic implants. The use of glutaraldehyde for fixing bioprosthetic tissue, however, has many significant disadvantages. Because glutaraldehyde tends to polymerize in solution, glutaraldehyde-fixed tissues are often characterized as having residual aldehyde groups associated with the fixed tissue.
Additionally, glutaraldehyde reacts with the free amines in the tissue to generate labile Schiff bases. Both the residual aldehydes and Schiff bases in glutaraldehyde-fixed tissues represent potential calcium binding sites that may lead to in viva calcification. Moreover, because glutaraldehyde is cytotoxic, it inhibits the desired cellular in-growth and integration of the implanted and glutaraldehyde-treated bioprosthetic tissue.
What is therefore needed are strategies that may be used in place of, or in conjunction with, glutaraldehyde fixation for mitigating some of the undesirable interactions between implanted bioprosthetic tissue and the host.